De Vry J, Benz U, Schreiber R, Traber J
Department of Psychopharmacology, Troponwerke, Cologne, Germany.
Eur J Pharmacol. 1993 Nov 16;249(3):331-9. doi: 10.1016/0014-2999(93)90530-u.
A putative animal model of anxiety based on shock-induced ultrasonic vocalization was pharmacologically validated in young adult rats. Suppression of shock-induced ultrasonic vocalization was obtained with diazepam, chlordiazepoxide, meprobamate and pentobarbital; the serotonin (5-HT)1A receptor agonists 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin], buspirone, ipsapirone, gepirone and tandospirone; the nonselective 5-HT receptor agonists TFMPP [1-(3-trifluoromethylphenyl)piperazin], mCPP [1-(3-chlorophenyl)piperazin] and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane); the NMDA antagonists PCP (phencyclidine) and MK-801; the alpha 2-adrenoceptor antagonists idazoxane, yohimbine and 1-PP (1-pyrimidinylpiperazine); and the atypical neuroleptic clozapine. The alpha 2-adrenoceptor agonist clonidine, the 5-HT2/5-HT1C antagonist ritanserin, the 5-HT3 antagonists ondansetron and ICS-205,930, and the 5-HT reuptake inhibitor fluoxetine did not, or only partially, reduce ultrasonic vocalization. Tricyclic and tetracyclic, as well as some atypical antidepressants and a monoamineoxidase (MAO) inhibitor, showed no ultrasonic vocalization reducing effects, or reduced ultrasonic vocalization only at high doses. An opiate, an antimuscarinic, (pro)convulsants and typical neuroleptics did not reduce ultrasonic vocalization. The present findings suggest that the ultrasonic vocalization model specifically measures anxiolytic effects. Because ultrasonic vocalization responding develops within five days, remains stable for at least three months and gives highly reproducible results, the test appears suitable for rapid and repeated testing of new anxiolytics in the same animals.
基于电击诱导超声发声建立的一种假定的焦虑动物模型，在年轻成年大鼠中得到了药理学验证。地西泮、氯氮卓、甲丙氨酯和戊巴比妥可抑制电击诱导的超声发声；5-羟色胺（5-HT）1A受体激动剂8-OH-DPAT [8-羟基-2-（二正丙基氨基）四氢萘]、丁螺环酮、伊沙匹隆、吉哌隆和坦度螺酮；非选择性5-HT受体激动剂TFMPP [1-（3-三氟甲基苯基）哌嗪]、mCPP [1-（3-氯苯基）哌嗪]和DOI（1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷）；NMDA拮抗剂苯环己哌啶（PCP）和MK-801；α2-肾上腺素能受体拮抗剂咪唑克生、育亨宾和1-PP（1-嘧啶基哌嗪）；以及非典型抗精神病药物氯氮平。α2-肾上腺素能受体激动剂可乐定、5-HT2/5-HT1C拮抗剂利坦色林、5-HT3拮抗剂昂丹司琼和ICS-205,930，以及5-HT再摄取抑制剂氟西汀未降低或仅部分降低超声发声。三环和四环类药物，以及一些非典型抗抑郁药和单胺氧化酶（MAO）抑制剂，未显示出降低超声发声的作用，或仅在高剂量时降低超声发声。阿片类药物、抗毒蕈碱药物、（促）惊厥药物和典型抗精神病药物未降低超声发声。目前的研究结果表明，超声发声模型可特异性地测量抗焦虑作用。由于超声发声反应在五天内形成，至少三个月保持稳定且结果具有高度可重复性，该试验似乎适用于在同一动物中对新型抗焦虑药物进行快速和重复测试。
